Immunosuppression as a consequence of malignancy is well-recognized however molecular factors from malignant tumors and cell receptors for these factors from the immune system are unknown. Immunosuppression in breast, kidney and squamous cell carcinomas is generally indicative of a poor prognosis for the patient suffering from these diseases. This project uses the same immunological tools as assays that have been used traditionally to study mechanisms of immunosuppression in T cells from individuals infected with human immunodeficiency virus type 1 (HIV-1). This year we discovered for the first time that several soluble factors extracted and/or secreted from human malignant tumors are capable of binding to recombinant soluble CD4, a cell surface receptor from T cells and the receptor used by the envelope protein from HIV in the step of the HIV infection process. In addition, CD40binding factors have been found in the sera of athymic mice that had received implants of human squamous cell carcinoma xenographs and in the media of SCC and U937 cell cultures. These CD4-binding soluble factors span a wide molecular weight range as judged by gel filtration chromatography and they could be also composed of proteolytic fragments from a few higher molecular weight intracellular proteins. In addition, the soluble factors compete with gp120 from HIV for the binding to CD4. This indicates that the soluble factors extracted from various malignant tumors are binding to CD4 the same way that gp120 binds to CD4. Studies are underway to evaluate the influence the cancer- derived CD4-binding factors have on T cell apoptosis and to compare these results to those previously found from studies on gp120-induced T cell apoptosis.